Microbial communities play important roles in human health and disease, are essential components of terrestrial and marine ecosystems, and are crucial for producing commercially valuable molecules in industrial processes. These communities consist of hundreds of species involved in complex interactions. Mapping the interrelationships between different species in a microbial community is vital for understanding and controlling ecosystem structure and function. Advances in sequencing and other omics technologies have led to thousands of datasets containing information about microbial composition, gene expression, and metabolism in microbial communities associated with human hosts and other environments. These provide valuable information in understanding how microbes interact with each other and how their interactions affect the health of their host (e.g., human or plant). Furthermore, understanding these interactions paves the way for the rational design and modulation of synthetic communities for producing antibiotics, biofuels, and pharmaceutical products. The first part of my thesis is focused on improving the workflow for the inference of microbial co-occurrence relationships from abundance data. Toward this goal, we developed Microbial Co-occurrence Network Explorer (MiCoNE), a pipeline that infers microbial co-occurrences from 16S ribosomal RNA (16S rRNA) amplicon data. This pipeline involves numerous complex steps that require specific tools and parameter choices, posing open questions about the robustness and uniqueness of the inferred networks. Through MiCoNE, we systematically analyzed how these choices of tools affect the final network and proposed guidelines on appropriate tool selection for a particular dataset. We envisage that this pipeline could be used to integrate multiple datasets and generate comparative analyses and consensus networks that can guide our understanding of microbial community assembly in different biomes. The second part of my thesis focuses on microbe-host interactions rather than microbe-microbe associations. In particular, we sought to predict the effects of microbial metabolites on human receptors and their associated regulatory pathways. We specifically focus on the Aryl hydrocarbon receptor (AHR), a ligand-mediated transcription factor involved in tumorigenesis. In this project, we aimed to systematically predict the binding of diverse microbial metabolites secreted from microorganisms found in the human oral microbiome to the AHR to identify links between the microbiome and cancer initiation. We further build a mathematical model of the AHR regulatory pathway and model the effects of ligand binding on downstream molecules. We envision that these methods could be used to predict the impact of microbial dysbioses on human regulatory pathways. In the final part of my thesis, we turn to the question of whether computational algorithms can help control microbial community growth to achieve specific objectives. In particular, we describe the development of a reinforcement learning algorithm to learn optimal environmental control strategies to steer a microbial community towards a certain goal, such as reaching a specific taxonomic distribution or producing desired metabolites. We train the reinforcement learning framework through community-level simulations of genome-scale metabolic models (GEMs) for different microbial species in bioreactor systems. In this project, we simulate a simple case study with two auxotrophic mutants to verify the algorithm's validity. Ultimately we aim to simulate the implementation of the algorithm in experimental bioreactor systems. Overall, the work presented in this thesis demonstrates how microbe-microbe and microbe-environment (including microbe-host) interactions represent plastic system-level properties whose understanding can help unravel the role of microbial communities in specific diseases. Correspondingly, manipulating these interactions, e.g., by appropriately modifying environmental conditions, can serve as a promising strategy for steering communities towards desired states, including producing valuable molecular products. / 2024-11-06T00:00:00Z

Esta pesquisa enfoca a avaliação do desempenho de nova configuração de unidade para tratamento biológico de esgoto sanitário por processo combinado, visando à remoção de nutrientes, especialmente nitrogênio. O sistema construído em escala piloto tem volume útil igual a 71,48 litros. Nesta nova configuração de reatores para tratamento terciário de esgoto sanitário, utilizaram-se três reatores sobrepostos, sendo: um reator UASB - “Upflow Anaerobic Sludge Blanket"; um reator de leito móvel e filme fixo aeróbio (com aplicação de oxigênio puro); e, um reator de leito móvel e filme fixo com ambiente anóxico. O material suporte utilizado nos reatores de leito móvel e filme fixo constituiu alternativa inédita no tratamento de efluentes líquidos. Foram utilizadas cavilhas “ranhuradas" de madeira, de dimensões aproximadas de 8,0 mm de diâmetro por 8,0 mm de comprimento. O desempenho geral do sistema quanto à remoção de matéria carbonácea e compostos nitrogenados, e as associações microbianas formadas nos três reatores são objetos principais de estudo deste trabalho. Foram obtidos resultados de remoção de DQO e de nitrogênio bastante satisfatórios, sobretudo quando o tempo de detenção hidráulica total esteve próximo a 20 horas, incluindo o compartimento de decantação (94,6 % para DQO; e 96,7 % para N-NTK, com formação de nitrato em concentrações inferiores a 10,0 mgN-NO3-/l). O TDH estudado variou entre 5 e 24 horas para os sistema completo. O estudo dos consórcios de microrganismos forneceu excelentes resultados quanto à quantidade, diversidade, e atividade das populações desenvolvidas nos diferentes ambientes, confirmando o bom desempenho do sistema e o fornecimento de ambiente adequado para o desenvolvimento das diferentes populações nos três reatores. A idealização desta configuração tem como finalidade realização de tratamento de esgoto sanitário até nível terciário em planta compacta, podendo ser utilizada por pequenas e grandes comunidades, devido à possibilidade de se construir diversos módulos do sistema proposto. / This research is focused on the performance evaluation of a new system configuration of combined biological reactors, treating domestic wastewater till tertiary level. The pilot scale proposed system had a total useful volume of 71,48 liters. This new configuration involves three types of superposed reactors: an Upflow Anaerobic Sludge Blanket reactor; an aerobic fixed film mobile bed reactor (fed with pure oxygen); and a fixed film mobile bed reactor at anoxic environment. The support material used inside the fixed film mobile bed reactors was wood made grooved dowels. The main purposes of this work are to evaluate the systems general performance regarding COD and nitrogen removal, and the microbial associations inside the reactors. It reached quite satisfactory results regarding COD and nitrogen removal when the total hydraulic retention time (HRT) was around 20 hours, including the clarification zone volume (94,6 % for the COD; and 96,7 % for the TKN-N, whit nitrate formation below 10,0 mgN-NO3-/l). HRTs from 5 to 20 hours were studied. The microbial associations were present in large number, with a great diversity and high specific activities at the different environments, confirming the good results obtained and the suitable environment provided for the growth of the different populations inside the three reactors. The idealization of this treatment system has the goal to treat domestic wastewater from small to large communities till tertiary level, in compact treatment plants, due to the possibility of constructing several modules of the system.

Esta pesquisa enfoca a avaliação do desempenho de nova configuração de unidade para tratamento biológico de esgoto sanitário por processo combinado, visando à remoção de nutrientes, especialmente nitrogênio. O sistema construído em escala piloto tem volume útil igual a 71,48 litros. Nesta nova configuração de reatores para tratamento terciário de esgoto sanitário, utilizaram-se três reatores sobrepostos, sendo: um reator UASB - “Upflow Anaerobic Sludge Blanket”; um reator de leito móvel e filme fixo aeróbio (com aplicação de oxigênio puro); e, um reator de leito móvel e filme fixo com ambiente anóxico. O material suporte utilizado nos reatores de leito móvel e filme fixo constituiu alternativa inédita no tratamento de efluentes líquidos. Foram utilizadas cavilhas “ranhuradas” de madeira, de dimensões aproximadas de 8,0 mm de diâmetro por 8,0 mm de comprimento. O desempenho geral do sistema quanto à remoção de matéria carbonácea e compostos nitrogenados, e as associações microbianas formadas nos três reatores são objetos principais de estudo deste trabalho. Foram obtidos resultados de remoção de DQO e de nitrogênio bastante satisfatórios, sobretudo quando o tempo de detenção hidráulica total esteve próximo a 20 horas, incluindo o compartimento de decantação (94,6 % para DQO; e 96,7 % para N-NTK, com formação de nitrato em concentrações inferiores a 10,0 mgN-NO3-/l). O TDH estudado variou entre 5 e 24 horas para os sistema completo. O estudo dos consórcios de microrganismos forneceu excelentes resultados quanto à quantidade, diversidade, e atividade das populações desenvolvidas nos diferentes ambientes, confirmando o bom desempenho do sistema e o fornecimento de ambiente adequado para o desenvolvimento das diferentes populações nos três reatores. A idealização desta configuração tem como finalidade realização de tratamento de esgoto sanitário até nível terciário em planta compacta, podendo ser utilizada por pequenas e grandes comunidades, devido à possibilidade de se construir diversos módulos do sistema proposto. / This research is focused on the performance evaluation of a new system configuration of combined biological reactors, treating domestic wastewater till tertiary level. The pilot scale proposed system had a total useful volume of 71,48 liters. This new configuration involves three types of superposed reactors: an Upflow Anaerobic Sludge Blanket reactor; an aerobic fixed film mobile bed reactor (fed with pure oxygen); and a fixed film mobile bed reactor at anoxic environment. The support material used inside the fixed film mobile bed reactors was wood made grooved dowels. The main purposes of this work are to evaluate the systems general performance regarding COD and nitrogen removal, and the microbial associations inside the reactors. It reached quite satisfactory results regarding COD and nitrogen removal when the total hydraulic retention time (HRT) was around 20 hours, including the clarification zone volume (94,6 % for the COD; and 96,7 % for the TKN-N, whit nitrate formation below 10,0 mgN-NO3-/l). HRTs from 5 to 20 hours were studied. The microbial associations were present in large number, with a great diversity and high specific activities at the different environments, confirming the good results obtained and the suitable environment provided for the growth of the different populations inside the three reactors. The idealization of this treatment system has the goal to treat domestic wastewater from small to large communities till tertiary level, in compact treatment plants, due to the possibility of constructing several modules of the system.